Dr Bird Flashcards
How do most tumours develop?
Develop in epithelium, then metastasise into the mesenchyme and then into the muscle
What are the properties of benign tumours?
- Develop in any tissue
- Grow locally
- May cause problems by pressure on brain or colon obstruction
- Histologically resemble the tissue of origin
- Do not spread to distant sites
What are the properties of in situ tumours?
- Usually develop in the epithelium
- Have altered histological appearance
- Variations in cell size and shape
- Do not invade basement membrane and supporting mesenchyme
What are the properties of cancers?
- Fully developed malignant tumours with the specific capacity to invade and destroy the underlying mesenchyme
- Metastasise
- Stimulate angiogenesis and development of blood supply
What does the ability to metastasise mean?
Can spread to other tissues
What are the exogenous agents that can cause mutations in DNA?
- Ionising radiation
- UV radiation
- Chemical carcinogens
- Viruses
What are the endogenous agents that can cause mutations in DNA?
- Errors in DNA replication
- Intrinsic instability
- Attack by free radicals
What is a transient mutation?
A mutation in DNA that can be repaired
How do tumours arise from mutations in DNA?
Permanent mutation occurs and cell division causes a tumour
What are the two broad classes of genes involved in the onset of cancer?
Proto-oncogenes and tumour suppressor genes
How are proto-oncogenes involved in the onset of cancer?
Excessively active in growth promotion
How are tumour suppressor genes?
Normally restrain cell growth but damage to these genes allows inappropriate growth
What is the effect of a point mutation?
Amino acid substitution
What is the effect of a frameshift mutation?
Scrambled sequence and truncated protein
What is the effect of a inappropriate expression or amplification mutation?
Normal protein at the wrong time or too much produced
What is the effect of a loss of gene mutation?
Loss of protein
What is the effect of a fusion with another gene mutation?
Chimeric protein with altered funtion
What is the effect of a epigenetic modification mutation?
Gene silencing and no protein
What is the effect of breakage of bonds between purine and deoxyribose?
Random base insertions
What is the effect of deamination of cytosine to uridine?
C -> U
What is the effect of deamination of methylcytosine to thymidine?
C -> T
What is the effect of ionising radiation on DNA?
Single and double stranded DNA breaks and damage from free radicals
What is the effect of UV radiation on DNA?
Thymidine dimers
What is the function of the p53 gene?
Surveys DNA for damage and elicits a repair
How is DNA damage caused by thymidine dimers repaired?
Removal of whole stretch of DNA and resynthesis using opposite strand as template
How is DNA damage caused by O-6 methyl guanine repaired?
Directly removed without breaking phosphate backbone
How is DNA damage caused by single strand breaks repaired?
Directly repaired
How is DNA damage caused by double strand breaks repaired?
Not easily repairable
What are the necessary properties for a tumour to spread?
- Self-sufficiency in growth signals
- Insensitivity to antigrowth signals
- Evasion of apoptosis
- Limitless replicative potential
- Tissue invasion and metastasis
- Sustained angiogenesis
What are growth signals generated by?
- Diffusible growth factors
- Extracellular matrix components
- Cell to cell adhesion molecules
What are examples of diffusible growth factors?
- EGF (Epidermal growth factor)
- FGF (Fibroblast growth factor)
- TGFa (Transforming growth factor alpha)
- PDGF (Platelet-derived growth factor)
What are the three ways in which cancer cells become growth signal autonomous?
- Modulation of growth factor provision
- Modulation of growth factor receptor activity
- Modulation of intracellular signalling pathways
What is the method of growth factor signalling?
- Growth factor binds to the receptor
- Receptor becomes active as a tyrosine kinase and autophosphorylates on tyrosine residues
- Some proteins can then dock with the receptor and become activated, others act as substrates for the receptor kinase and become phosphorylated (Usually protein kinases)
- Phosphorylated protein then activates a transcription factor
How does modulation of growth factor receptor activity cause cancer cells self sufficiency in growth signals?
Overexpression of the growth factor allows tumours to respond to low levels of growth factor that would not normally produce a growth response
